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Novel synthetic polymyxins kill Gram-positive bacteria

Authors :
Miguel Viñas
Josep M. Sierra
Isabel Pérez-Guillén
Teresa Vinuesa
Francesc Rabanal
Héctor Rudilla
Source :
Dipòsit Digital de la UB, Universidad de Barcelona
Publication Year :
2018
Publisher :
Oxford University Press, 2018.

Abstract

Background Staphylococcus aureus, including 'superbug' MRSA, is a major cause of nosocomial infections. In the European Union, up to 171 200 new nosocomial MRSA infections are acquired annually, and in the USA S. aureus causes more deaths than HIV/AIDS and tuberculosis combined. MRSA is also the first group of pathogens that infect the pulmonary tract in young patients with cystic fibrosis. Objectives We describe two newly developed and synthesized colistin (polymyxin E)-inspired molecules. Methods A collection of several isolates of S. aureus [including MRSA and vancomycin-resistant S. aureus (VRSA)] was tested. To check the antimicrobial activity, we performed time-kill curves, growth curves, biofilm eradication, toxicity and isothermal titration calorimetry. Results Both peptides showed high antimicrobial activities (MIC 4 mg/L) and low relative toxicities (selectivity index close to 23). Conclusions Successful production of polymyxin-scaffold molecules active against S. aureus, both MRSA and VRSA, opens up new approaches to the treatment of these complicated infections.

Details

Database :
OpenAIRE
Journal :
Dipòsit Digital de la UB, Universidad de Barcelona
Accession number :
edsair.doi.dedup.....0a677feed93096026315a5dc46069753